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Basic Science and Pathogenesis.

Tomas Kavanagh1, Stephanie Trgovcevic1, Laura Nementzik1

  • 1The University of Sydney, Sydney, NSW, Australia.

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|December 25, 2025
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Summary
This summary is machine-generated.

This study reveals distinct protein solubility changes in primary tauopathies like corticobasal degeneration (CBD), Pick's disease (PiD), and progressive supranuclear palsy (PSP). Findings offer insights into disease mechanisms and potential biomarkers for tauopathies.

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Area of Science:

  • Neuroscience
  • Proteomics
  • Biochemistry

Background:

  • Primary tauopathies (CBD, PiD, PSP) involve distinct tau aggregation patterns.
  • Protein alterations beyond tau in these neurodegenerative diseases are not well understood.

Purpose of the Study:

  • To comparatively analyze protein solubility across different primary tauopathies.
  • To identify disease-specific proteomic signatures and underlying mechanisms.

Main Methods:

  • Sarkosyl fractionation of post-mortem frontal cortex from CBD, PiD, and PSP cases.
  • Mass spectrometry to profile protein abundance and solubility.
  • Gene set enrichment analysis and bicorrelation to identify dysregulated pathways and protein associations with tau.

Main Results:

  • Tau isoforms show disease-specific solubility.
  • PSP exhibited more distinct protein solubility changes (78 proteins) compared to CBD and PiD (6 proteins).
  • Key changes observed in lysosomal regulators, postsynaptic proteins, extracellular matrix, and mitochondrial proteins.
  • S100B elevated in CBD and PiD soluble fractions, indicating greater cellular distress.
  • MOBP strongly correlated with tau in PiD.

Conclusions:

  • This study presents the first comparative proteomic solubility analysis across tauopathies.
  • Revealed disease-specific signatures and divergent pathogenic mechanisms.
  • Identified key proteins and pathways linked to tau pathology, suggesting potential biomarkers.